public bool allowed_relation(Proteoform pf1, Proteoform pf2_with_allowed_lysines, ProteoformComparison relation_type)
{
if (relation_type == ProteoformComparison.ExperimentalTheoretical || relation_type == ProteoformComparison.ExperimentalDecoy)
{
return
((pf1.modified_mass - pf2_with_allowed_lysines.modified_mass) >=
Sweet.lollipop.et_low_mass_difference &&
(pf1.modified_mass - pf2_with_allowed_lysines.modified_mass) <=
Sweet.lollipop.et_high_mass_difference &&
(Sweet.lollipop.add_td_theoreticals || !(pf2_with_allowed_lysines as TheoreticalProteoform).new_topdown_proteoform));
}
else if (relation_type == ProteoformComparison.ExperimentalExperimental)
{
return
(pf1 != pf2_with_allowed_lysines &&
pf1.modified_mass >= pf2_with_allowed_lysines.modified_mass &&
pf1 != pf2_with_allowed_lysines &&
pf1.modified_mass - pf2_with_allowed_lysines.modified_mass <= Sweet.lollipop.ee_max_mass_difference &&
Math.Abs((pf1 as ExperimentalProteoform).agg_rt - (pf2_with_allowed_lysines as ExperimentalProteoform).agg_rt) <= Sweet.lollipop.ee_max_RetentionTime_difference);
}
else if (relation_type == ProteoformComparison.ExperimentalFalse)
{
//going to hard code in 10 minutes as min RT for 2 to not be related.
return
(pf1.modified_mass >= pf2_with_allowed_lysines.modified_mass &&
pf1 != pf2_with_allowed_lysines &&
(pf1.modified_mass - pf2_with_allowed_lysines.modified_mass <= Sweet.lollipop.ee_max_mass_difference) &&
(Sweet.lollipop.neucode_labeled || Math.Abs((pf1 as ExperimentalProteoform).agg_rt - (pf2_with_allowed_lysines as ExperimentalProteoform).agg_rt) > 10) &&
(!Sweet.lollipop.neucode_labeled || Math.Abs((pf1 as ExperimentalProteoform).agg_rt - (pf2_with_allowed_lysines as ExperimentalProteoform).agg_rt) < Sweet.lollipop.ee_max_RetentionTime_difference));
}
else
{
return(false);
}
}
public bool allowed_relation(Proteoform pf1, Proteoform pf2, ProteoformComparison relation_type)
{
switch (relation_type)
{
case (ProteoformComparison.ExperimentalTheoretical):
case (ProteoformComparison.ExperimentalDecoy):
return((!SaveState.lollipop.neucode_labeled || pf2.lysine_count == pf1.lysine_count) &&
(pf1.modified_mass - pf2.modified_mass) >= SaveState.lollipop.et_low_mass_difference &&
(pf1.modified_mass - pf2.modified_mass) <= SaveState.lollipop.et_high_mass_difference &&
(pf2.ptm_set.ptm_combination.Count < 3 || pf2.ptm_set.ptm_combination.Select(ptm => ptm.modification.monoisotopicMass).All(x => x == pf2.ptm_set.ptm_combination.First().modification.monoisotopicMass)));
case (ProteoformComparison.ExperimentalExperimental):
return(pf1.modified_mass >= pf2.modified_mass &&
pf1 != pf2 &&
(!SaveState.lollipop.neucode_labeled || pf1.lysine_count == pf2.lysine_count) &&
pf1.modified_mass - pf2.modified_mass <= SaveState.lollipop.ee_max_mass_difference &&
Math.Abs(((ExperimentalProteoform)pf1).agg_rt - ((ExperimentalProteoform)pf2).agg_rt) <= SaveState.lollipop.ee_max_RetentionTime_difference);
case (ProteoformComparison.ExperimentalFalse):
return(pf1.modified_mass >= pf2.modified_mass &&
pf1 != pf2 &&
(pf1.modified_mass - pf2.modified_mass <= SaveState.lollipop.ee_max_mass_difference) &&
(!SaveState.lollipop.neucode_labeled || Math.Abs(pf1.lysine_count - pf2.lysine_count) > SaveState.lollipop.missed_lysines) &&
(SaveState.lollipop.neucode_labeled || Math.Abs(((ExperimentalProteoform)pf1).agg_rt - ((ExperimentalProteoform)pf2).agg_rt) > SaveState.lollipop.ee_max_RetentionTime_difference * 2) &&
(!SaveState.lollipop.neucode_labeled || Math.Abs(((ExperimentalProteoform)pf1).agg_rt - ((ExperimentalProteoform)pf2).agg_rt) < SaveState.lollipop.ee_max_RetentionTime_difference));
default:
return(false);
}
}
private void assign_pf_identity(ExperimentalProteoform e, Proteoform theoretical_reference, PtmSet set, ProteoformRelation r, int sign, PtmSet change)
{
if (r.represented_ptmset == null)
{
r.represented_ptmset = change;
if (r.RelationType == ProteoformComparison.ExperimentalExperimental)
{
r.DeltaMass *= sign;
}
}
if (e.linked_proteoform_references == null)
{
e.linked_proteoform_references = new List <Proteoform>(this.linked_proteoform_references);
e.linked_proteoform_references.Add(this);
e.ptm_set = set;
}
if (e.gene_name == null)
{
e.gene_name = this.gene_name;
}
else
{
e.gene_name.gene_names.Concat(this.gene_name.gene_names);
}
}
public bool allowed_relation(Proteoform pf1, Proteoform pf2_with_allowed_lysines, ProteoformComparison relation_type)
{
if (relation_type == ProteoformComparison.ExperimentalTheoretical || relation_type == ProteoformComparison.ExperimentalDecoy)
{
return
((pf1.modified_mass - pf2_with_allowed_lysines.modified_mass) >= Sweet.lollipop.et_low_mass_difference &&
(pf1.modified_mass - pf2_with_allowed_lysines.modified_mass) <= Sweet.lollipop.et_high_mass_difference);
}
else if (relation_type == ProteoformComparison.ExperimentalExperimental)
{
return
(pf1 != pf2_with_allowed_lysines &&
pf1.modified_mass >= pf2_with_allowed_lysines.modified_mass &&
pf1 != pf2_with_allowed_lysines &&
pf1.modified_mass - pf2_with_allowed_lysines.modified_mass <= Sweet.lollipop.ee_max_mass_difference &&
Math.Abs((pf1 as ExperimentalProteoform).agg_rt - (pf2_with_allowed_lysines as ExperimentalProteoform).agg_rt) <= Sweet.lollipop.ee_max_RetentionTime_difference);
}
else if (relation_type == ProteoformComparison.ExperimentalFalse)
{
return
(pf1.modified_mass >= pf2_with_allowed_lysines.modified_mass &&
pf1 != pf2_with_allowed_lysines &&
(pf1.modified_mass - pf2_with_allowed_lysines.modified_mass <= Sweet.lollipop.ee_max_mass_difference) &&
(Sweet.lollipop.neucode_labeled || Math.Abs((pf1 as ExperimentalProteoform).agg_rt - (pf2_with_allowed_lysines as ExperimentalProteoform).agg_rt) > Sweet.lollipop.ee_max_RetentionTime_difference * 2) &&
(!Sweet.lollipop.neucode_labeled || Math.Abs((pf1 as ExperimentalProteoform).agg_rt - (pf2_with_allowed_lysines as ExperimentalProteoform).agg_rt) < Sweet.lollipop.ee_max_RetentionTime_difference));
}
else
{
return(false);
}
}
public static string get_proteoform_shared_name(Proteoform p, string node_label, int double_rounding)
{
if (p as ExperimentalProteoform != null)
{
ExperimentalProteoform e = p as ExperimentalProteoform;
string name = Math.Round(e.agg_mass, double_rounding) + "_Da_" + e.accession;
if (node_label == Lollipop.node_labels[1] && e.linked_proteoform_references != null && e.linked_proteoform_references.Count > 0)
{
name += " " + (e.linked_proteoform_references.First() as TheoreticalProteoform).accession
+ " " + (e.ptm_set.ptm_combination.Count == 0 ?
"Unmodified" :
String.Join("; ", e.ptm_set.ptm_combination.Select(ptm => SaveState.lollipop.theoretical_database.unlocalized_lookup[ptm.modification].id)));
}
return(name);
}
else if (p as TheoreticalProteoform != null)
{
return(p.accession + " " + p.ptm_description);
}
else
{
return(p.accession);
}
}
private static PtmSet determine_mod_change(ExperimentalProteoform e, Proteoform p, TheoreticalProteoform theoretical_base, ProteoformRelation r, PtmSet this_ptmset)
{
double mass_tolerance = p.modified_mass / 1000000 * Sweet.lollipop.mass_tolerance;
int sign = Math.Sign(e.modified_mass - p.modified_mass);
double deltaM = Math.Sign(r.peak.DeltaMass) < 0 ? r.peak.DeltaMass : sign * r.peak.DeltaMass; // give EE relations the correct sign, but don't switch negative ET relation deltaM's
List <PtmSet> possible_additions = r.peak.possiblePeakAssignments.Where(peak => Math.Abs(peak.mass - deltaM) <= 1).ToList(); // EE relations have PtmSets around both positive and negative deltaM, so remove the ones around the opposite of the deltaM of interest
PtmSet best_addition = generate_possible_added_ptmsets(possible_additions, Sweet.lollipop.theoretical_database.all_mods_with_mass, theoretical_base, p.begin, p.end, p.ptm_set, 1, true)
.OrderBy(x => (double)x.ptm_rank_sum + Math.Abs(x.mass - deltaM) * 10E-6) // major score: delta rank; tie breaker: deltaM, where it's always less than 1
.FirstOrDefault();
PtmSet best_loss = null;
foreach (PtmSet set in Sweet.lollipop.theoretical_database.all_possible_ptmsets)
{
bool within_loss_tolerance = deltaM >= -set.mass - mass_tolerance && deltaM <= -set.mass + mass_tolerance;
List <Modification> these_mods = this_ptmset.ptm_combination.Select(ptm => ptm.modification).ToList();
List <Modification> those_mods = set.ptm_combination.Select(ptm => ptm.modification).ToList(); // all must be in the current set to remove them
bool can_be_removed = those_mods.All(m1 => these_mods.Count(m2 => m2.OriginalId == m1.OriginalId) >= those_mods.Count(m2 => m2.OriginalId == m1.OriginalId)); //# of each mod in current set must be greater than or equal to # in set to remove.
bool better_than_current_best_loss = best_loss == null || Math.Abs(deltaM - (-set.mass)) < Math.Abs(deltaM - (-best_loss.mass));
if (can_be_removed && within_loss_tolerance && better_than_current_best_loss)
{
best_loss = set;
}
}
if (best_addition == null && best_loss == null)
{
return(null);
}
// Make the new ptmset with ptms removed or added
PtmSet with_mod_change = null;
if (best_loss == null)
{
with_mod_change = new PtmSet(new List <Ptm>(this_ptmset.ptm_combination.Concat(best_addition.ptm_combination).Where(ptm => ptm.modification.MonoisotopicMass != 0).ToList()));
}
else
{
List <Ptm> new_combo = new List <Ptm>(this_ptmset.ptm_combination);
foreach (Ptm ptm in best_loss.ptm_combination)
{
new_combo.Remove(new_combo.FirstOrDefault(asdf => asdf.modification.Equals(ptm.modification)));
}
with_mod_change = new PtmSet(new_combo);
}
if (r.represented_ptmset == null)
{
r.represented_ptmset = best_loss == null ? best_addition : best_loss;
if (r.RelationType == ProteoformComparison.ExperimentalExperimental)
{
r.DeltaMass *= sign;
}
}
return(with_mod_change);
}
public List <ProteoformFamily> construct_families()
{
ProteoformFamily.reset_family_counter();
Stack <Proteoform> remaining = new Stack <Proteoform>(this.experimental_proteoforms.ToArray());
List <ProteoformFamily> running_families = new List <ProteoformFamily>();
List <Proteoform> running = new List <Proteoform>();
List <Thread> active = new List <Thread>();
while (remaining.Count > 0 || active.Count > 0)
{
while (remaining.Count > 0 && active.Count < Environment.ProcessorCount)
{
Proteoform root = remaining.Pop();
ProteoformFamily fam = new ProteoformFamily(root);
Thread t = new Thread(new ThreadStart(fam.construct_family));
t.Start();
running_families.Add(fam);
running.Add(root);
active.Add(t);
}
foreach (Thread t in active)
{
t.Join();
}
List <Proteoform> cumulative_proteoforms = new List <Proteoform>();
foreach (ProteoformFamily family in running_families.ToList())
{
if (cumulative_proteoforms.Contains(family.proteoforms.First()))
{
running_families.Remove(family); // check for duplicates due to arbitrary seed selection
}
else
{
cumulative_proteoforms.AddRange(family.proteoforms);
Parallel.ForEach(family.proteoforms, p => { lock (p) p.family = family; });
}
}
this.families.AddRange(running_families);
remaining = new Stack <Proteoform>(remaining.Except(cumulative_proteoforms));
running_families.Clear();
running.Clear();
active.Clear();
}
if (Sweet.lollipop.gene_centric_families)
{
families = combine_gene_families(families).ToList();
}
Sweet.lollipop.theoretical_database.aaIsotopeMassList = new AminoAcidMasses(Sweet.lollipop.carbamidomethylation, Sweet.lollipop.neucode_labeled).AA_Masses;
Parallel.ForEach(families, f => f.identify_experimentals());
return(families);
}
public List <ProteoformFamily> construct_families()
{
Stack <Proteoform> remaining = new Stack <Proteoform>(this.experimental_proteoforms.Where(e => e.accepted).ToArray());
List <ProteoformFamily> running_families = new List <ProteoformFamily>();
List <Proteoform> running = new List <Proteoform>();
List <Thread> active = new List <Thread>();
while (remaining.Count > 0 || active.Count > 0)
{
while (remaining.Count > 0 && active.Count < Environment.ProcessorCount)
{
Proteoform root = remaining.Pop();
ProteoformFamily fam = new ProteoformFamily(root);
Thread t = new Thread(new ThreadStart(fam.construct_family));
t.Start();
running_families.Add(fam);
running.Add(root);
active.Add(t);
}
foreach (Thread t in active)
{
t.Join();
}
List <Proteoform> cumulative_proteoforms = new List <Proteoform>();
foreach (ProteoformFamily family in running_families.ToList())
{
if (cumulative_proteoforms.Contains(family.proteoforms.First()))
{
running_families.Remove(family); // check for duplicates due to arbitrary seed selection
}
else
{
cumulative_proteoforms.AddRange(family.proteoforms);
Parallel.ForEach(family.proteoforms, p => { lock (p) p.family = family; });
}
}
this.families.AddRange(running_families);
remaining = new Stack <Proteoform>(remaining.Except(cumulative_proteoforms));
running_families.Clear();
running.Clear();
active.Clear();
}
if (gene_centric_families)
{
families = combine_gene_families(families).ToList();
}
Parallel.ForEach(families, f => f.identify_experimentals());
return(families);
}
public bool shift_experimental_masses(int shift, bool neucode_labeled)
{
if (RelationType != ProteoformComparison.ExperimentalTheoretical)
{
return(false); //Not currently intended for ee relations
}
foreach (ProteoformRelation r in this.grouped_relations)
{
Proteoform p = r.connected_proteoforms[0];
if (p is ExperimentalProteoform && ((ExperimentalProteoform)p).mass_shifted == false && SaveState.lollipop.target_proteoform_community.experimental_proteoforms.Contains(p))
{
((ExperimentalProteoform)p).shift_masses(shift, neucode_labeled);
}
}
return(true);
}
public ProteoformRelation(Proteoform pf1, Proteoform pf2, ProteoformComparison relation_type, double delta_mass, string current_directory)
{
connected_proteoforms[0] = pf1;
connected_proteoforms[1] = pf2;
RelationType = relation_type;
DeltaMass = delta_mass;
InstanceId = instanceCounter;
lock (SaveState.lollipop) instanceCounter += 1; //Not thread safe
if (CH2 == null || HPO3 == null)
{
Loaders.LoadElements(Path.Combine(current_directory, "elements.dat"));
CH2 = ChemicalFormula.ParseFormula("C1 H2");
HPO3 = ChemicalFormula.ParseFormula("H1 O3 P1");
}
if (SaveState.lollipop.neucode_labeled)
{
lysine_count = pf1.lysine_count;
}
if ((relation_type == ProteoformComparison.ExperimentalTheoretical || relation_type == ProteoformComparison.ExperimentalDecoy) &&
SaveState.lollipop.theoretical_database.possible_ptmset_dictionary.TryGetValue(Math.Round(delta_mass, 1), out List <PtmSet> candidate_sets) &&
pf2 as TheoreticalProteoform != null)
{
TheoreticalProteoform t = pf2 as TheoreticalProteoform;
double mass_tolerance = t.modified_mass / 1000000 * (double)SaveState.lollipop.mass_tolerance;
List <PtmSet> narrower_range_of_candidates = candidate_sets.Where(s => Math.Abs(s.mass - delta_mass) < 0.05).ToList();
candidate_ptmset = t.generate_possible_added_ptmsets(narrower_range_of_candidates, delta_mass, mass_tolerance, SaveState.lollipop.theoretical_database.all_mods_with_mass, t, t.sequence, SaveState.lollipop.mod_rank_first_quartile)
.OrderBy(x => x.ptm_rank_sum + Math.Abs(Math.Abs(x.mass) - Math.Abs(delta_mass)) * 10E-6) // major score: delta rank; tie breaker: deltaM, where it's always less than 1
.FirstOrDefault();
}
// Start the model (0 Da) at the mass defect of CH2 or HPO3 itself, allowing the peak width tolerance on either side
double half_peak_width = RelationType == ProteoformComparison.ExperimentalTheoretical || RelationType == ProteoformComparison.ExperimentalDecoy ?
SaveState.lollipop.peak_width_base_et / 2 :
SaveState.lollipop.peak_width_base_ee / 2;
double low_decimal_bound = half_peak_width + ((CH2.MonoisotopicMass - Math.Truncate(CH2.MonoisotopicMass)) / CH2.MonoisotopicMass) * (Math.Abs(delta_mass) <= CH2.MonoisotopicMass ? CH2.MonoisotopicMass : Math.Abs(delta_mass));
double high_decimal_bound = 1 - half_peak_width + ((HPO3.MonoisotopicMass - Math.Ceiling(HPO3.MonoisotopicMass)) / HPO3.MonoisotopicMass) * (Math.Abs(delta_mass) <= HPO3.MonoisotopicMass ? HPO3.MonoisotopicMass : Math.Abs(delta_mass));
double delta_mass_decimal = Math.Abs(delta_mass - Math.Truncate(delta_mass));
outside_no_mans_land = delta_mass_decimal <= low_decimal_bound || delta_mass_decimal >= high_decimal_bound ||
high_decimal_bound <= low_decimal_bound;
}
public ProteoformFamily(Proteoform seed)
{
family_counter++;
this.family_id = family_counter;
this.seed = seed;
}
private void get_uniprot_mods()
{
var mods = topdown_ptm_set.ptm_combination.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
topdown_uniprot_mods = "";
string add = "";
if (Sweet.lollipop.theoretical_database.theoreticals_by_accession.ContainsKey(Sweet.lollipop.target_proteoform_community.community_number))
{
Sweet.lollipop.theoretical_database.theoreticals_by_accession[Sweet.lollipop.target_proteoform_community.community_number].TryGetValue(accession.Split('_')[0].Split('-')[0], out var matching_theoretical);
if (matching_theoretical != null)
{
foreach (string mod in mods)
{
// positions with mod
List <int> theo_ptms = matching_theoretical.First().ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= topdown_begin && p.Key <= topdown_end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (topdown_ptm_set.ptm_combination.Where(ptm => !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
topdown_novel_mods = true;
}
}
topdown_uniprot_mods += add;
if (add.Length == 0)
{
topdown_uniprot_mods += "N/A";
}
foreach (var ambig_id in ambiguous_topdown_hits)
{
Sweet.lollipop.theoretical_database.theoreticals_by_accession[Sweet.lollipop.target_proteoform_community.community_number].TryGetValue(accession.Split('_')[0].Split('-')[0], out var matching_ambig_theoretical);
if (matching_ambig_theoretical != null)
{
var ambig_mods = ambig_id.ptm_list.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
topdown_uniprot_mods += " | ";
add = "";
foreach (var mod in ambig_mods)
{
// positions with mod
List <int> theo_ptms = matching_ambig_theoretical.First().ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= ambig_id.begin && p.Key <= ambig_id.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (ambig_id.ptm_list.Where(ptm => !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
topdown_novel_mods = true;
}
}
}
topdown_uniprot_mods += add;
if (add.Length == 0)
{
topdown_uniprot_mods += "N/A";
}
}
}
}
}
public List <ProteoformFamily> construct_families()
{
ProteoformFamily.reset_family_counter();
Stack <Proteoform> remaining = new Stack <Proteoform>(this.experimental_proteoforms.Where(e => e.accepted).ToArray());
List <ProteoformFamily> running_families = new List <ProteoformFamily>();
List <Proteoform> running = new List <Proteoform>();
List <Thread> active = new List <Thread>();
while (remaining.Count > 0 || active.Count > 0)
{
while (remaining.Count > 0 && active.Count < Environment.ProcessorCount)
{
Proteoform root = remaining.Pop();
ProteoformFamily fam = new ProteoformFamily(root);
Thread t = new Thread(new ThreadStart(fam.construct_family));
t.Start();
running_families.Add(fam);
running.Add(root);
active.Add(t);
}
foreach (Thread t in active)
{
t.Join();
}
List <Proteoform> cumulative_proteoforms = new List <Proteoform>();
foreach (ProteoformFamily family in running_families.ToList())
{
if (cumulative_proteoforms.Contains(family.proteoforms.First()))
{
running_families.Remove(family); // check for duplicates due to arbitrary seed selection
}
else
{
cumulative_proteoforms.AddRange(family.proteoforms);
Parallel.ForEach(family.proteoforms, p => { lock (p) p.family = family; });
}
}
this.families.AddRange(running_families);
remaining = new Stack <Proteoform>(remaining.Except(cumulative_proteoforms));
running_families.Clear();
running.Clear();
active.Clear();
}
if (Lollipop.gene_centric_families)
{
families = combine_gene_families(families).ToList();
}
Sweet.lollipop.theoretical_database.aaIsotopeMassList = new AminoAcidMasses(Sweet.lollipop.carbamidomethylation, Sweet.lollipop.neucode_labeled).AA_Masses;
Parallel.ForEach(families, f => f.identify_experimentals());
//read in BU results if available, map to proteoforms.
//Sweet.lollipop.BottomUpPSMList.Clear();
//BottomUpReader.bottom_up_PTMs_not_in_dictionary.Clear();
//foreach (InputFile file in Sweet.lollipop.input_files.Where(f => f.purpose == Purpose.BottomUp))
//{
// Sweet.lollipop.BottomUpPSMList.AddRange(BottomUpReader.ReadBUFile(file.complete_path, theoreticals_by_accession.Values.ToList()));
//}
return(families);
}
public ProteoformRelation(Proteoform pf1, Proteoform pf2, ProteoformComparison relation_type, double delta_mass, string current_directory)
{
connected_proteoforms[0] = pf1;
connected_proteoforms[1] = pf2;
RelationType = relation_type;
DeltaMass = delta_mass;
InstanceId = instanceCounter;
lock (Sweet.lollipop) instanceCounter += 1; //Not thread safe
if (CH2 == null || HPO3 == null)
{
CH2 = ChemicalFormula.ParseFormula("C1 H2");
HPO3 = ChemicalFormula.ParseFormula("H1 O3 P1");
}
if (Sweet.lollipop.neucode_labeled)
{
lysine_count = pf1.lysine_count;
}
List <PtmSet> candidate_sets = new List <PtmSet>();
if (Sweet.lollipop.et_use_notch && (relation_type == ProteoformComparison.ExperimentalTheoretical || relation_type == ProteoformComparison.ExperimentalDecoy))
{
if (Sweet.lollipop.et_use_notch && !Sweet.lollipop.et_notch_ppm)
{
double mass = delta_mass - Sweet.lollipop.notch_tolerance_et;
while (mass <= delta_mass + Sweet.lollipop.notch_tolerance_et)
{
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary_notches.TryGetValue(
Math.Round(mass, 1), out List <PtmSet> candidates);
if (candidates != null)
{
candidate_sets.AddRange(candidates);
}
mass += 0.1;
}
candidate_sets = candidate_sets.Distinct().ToList();
}
else
{
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary_notches.TryGetValue(Math.Round(delta_mass, 1), out candidate_sets);
}
if (candidate_sets != null)
{
candidate_sets = candidate_sets.Where(s => Sweet.lollipop.et_notch_ppm
? Math.Abs(s.mass - delta_mass) * 1e6 / pf1.modified_mass <
Sweet.lollipop.notch_tolerance_et
: Math.Abs(s.mass - delta_mass) < Sweet.lollipop.notch_tolerance_et).ToList();
candidate_ptmset = candidate_sets.OrderBy(s => s.ptm_rank_sum).FirstOrDefault();
}
}
else if (Sweet.lollipop.ee_use_notch &&
(relation_type == ProteoformComparison.ExperimentalExperimental ||
relation_type == ProteoformComparison.ExperimentalFalse))
{
if (Sweet.lollipop.ee_use_notch && !Sweet.lollipop.ee_notch_ppm)
{
double mass = delta_mass - Sweet.lollipop.notch_tolerance_ee;
while (mass <= delta_mass + Sweet.lollipop.notch_tolerance_ee)
{
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary_notches.TryGetValue(
Math.Round(mass, 1), out List <PtmSet> candidates);
if (candidates != null)
{
candidate_sets.AddRange(candidates);
}
mass += 0.1;
}
candidate_sets = candidate_sets.Distinct().ToList();
}
else
{
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary_notches.TryGetValue(Math.Round(delta_mass, 1), out candidate_sets);
}
if (candidate_sets != null)
{
candidate_sets = candidate_sets.Where(s => Sweet.lollipop.ee_notch_ppm
? Math.Abs(s.mass - delta_mass) * 1e6 / pf1.modified_mass <
Sweet.lollipop.notch_tolerance_ee
: Math.Abs(s.mass - delta_mass) < Sweet.lollipop.notch_tolerance_ee).ToList();
candidate_ptmset = candidate_sets.OrderBy(s => s.ptm_rank_sum).FirstOrDefault();
}
}
else if
(relation_type == ProteoformComparison.ExperimentalTheoretical ||
relation_type == ProteoformComparison.ExperimentalDecoy)
{
if (Sweet.lollipop.peak_width_base_et > 0.09)
{
double mass = delta_mass - Sweet.lollipop.peak_width_base_et;
while (mass <= delta_mass + Sweet.lollipop.peak_width_base_et)
{
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary.TryGetValue(
Math.Round(mass, 1), out List <PtmSet> candidates);
if (candidates != null)
{
candidate_sets.AddRange(candidates);
}
mass += 0.1;
}
candidate_sets = candidate_sets.Distinct().ToList();
}
else
{
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary.TryGetValue(
Math.Round(delta_mass, 1), out candidate_sets);
}
if (pf2 as TheoreticalProteoform != null && candidate_sets != null && candidate_sets.Count > 0)
{
List <PtmSet> narrower_range_of_candidates = new List <PtmSet>();
if (Sweet.lollipop.et_use_notch)
{
narrower_range_of_candidates = candidate_sets;
}
else
{
narrower_range_of_candidates = candidate_sets
.Where(s => Math.Abs(s.mass - delta_mass) < Sweet.lollipop.peak_width_base_et).ToList();
}
TheoreticalProteoform t = pf2 as TheoreticalProteoform;
candidate_ptmset = Proteoform.generate_possible_added_ptmsets(narrower_range_of_candidates,
Sweet.lollipop.theoretical_database.all_mods_with_mass, t, pf2.begin, pf2.end,
pf2.ptm_set,
Sweet.lollipop.mod_rank_first_quartile, false).OrderBy(x =>
x.ptm_rank_sum +
Math.Abs(Math.Abs(x.mass) - Math.Abs(delta_mass)) *
10E-6) // major score: delta rank; tie breaker: deltaM, where it's always less than 1
.FirstOrDefault();
}
}
// Start the model (0 Da) at the mass defect of CH2 or HPO3 itself, allowing the peak width tolerance on either side
double half_peak_width = RelationType == ProteoformComparison.ExperimentalTheoretical || RelationType == ProteoformComparison.ExperimentalDecoy ?
Sweet.lollipop.peak_width_base_et / 2 :
Sweet.lollipop.peak_width_base_ee / 2;
double low_decimal_bound = half_peak_width + ((CH2.MonoisotopicMass - Math.Truncate(CH2.MonoisotopicMass)) / CH2.MonoisotopicMass) * (Math.Abs(delta_mass) <= CH2.MonoisotopicMass ? CH2.MonoisotopicMass : Math.Abs(delta_mass));
double high_decimal_bound = 1 - half_peak_width + ((HPO3.MonoisotopicMass - Math.Ceiling(HPO3.MonoisotopicMass)) / HPO3.MonoisotopicMass) * (Math.Abs(delta_mass) <= HPO3.MonoisotopicMass ? HPO3.MonoisotopicMass : Math.Abs(delta_mass));
double delta_mass_decimal = Math.Abs(delta_mass - Math.Truncate(delta_mass));
outside_no_mans_land = delta_mass_decimal <= low_decimal_bound || delta_mass_decimal >= high_decimal_bound ||
high_decimal_bound <= low_decimal_bound;
if (Sweet.lollipop.et_use_notch && (relation_type == ProteoformComparison.ExperimentalTheoretical || relation_type == ProteoformComparison.ExperimentalDecoy))
{
outside_no_mans_land = true;
}
if (Sweet.lollipop.ee_use_notch && (relation_type == ProteoformComparison.ExperimentalExperimental || relation_type == ProteoformComparison.ExperimentalFalse))
{
outside_no_mans_land = true;
}
}
private void assign_pf_identity(ExperimentalProteoform e, PtmSet set, ProteoformRelation r, TheoreticalProteoform theoretical_base)
{
if (e.linked_proteoform_references == null)
{
e.linked_proteoform_references = new List <Proteoform>(this.linked_proteoform_references);
e.linked_proteoform_references.Add(this);
e.ptm_set = set;
e.begin = this.begin;
e.end = this.end;
List <Ptm> remove = new List <Ptm>();
//do retention of M first
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "AminoAcid"))
{
e.begin--;
remove.Add(mod);
}
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "Missing"))
{
if (theoretical_base.sequence[this.begin - theoretical_base.begin].ToString() == mod.modification.Target.ToString())
{
e.begin++;
remove.Add(mod); //dont have in ptmset --> change the begin & end
}
else if (theoretical_base.sequence[this.end - this.begin].ToString() == mod.modification.Target.ToString())
{
e.end--;
remove.Add(mod);
}
}
foreach (var ptm in remove)
{
e.ptm_set.ptm_combination.Remove(ptm);
}
e.ptm_set = new PtmSet(e.ptm_set.ptm_combination);
if (e.gene_name == null)
{
e.gene_name = this.gene_name;
}
else if (!e.topdown_id)
{
e.gene_name.gene_names.Concat(this.gene_name.gene_names);
}
}
else
{
//check if assign
int begin = this.begin;
int end = this.end;
PtmSet ptm_set = set;
List <Ptm> remove = new List <Ptm>();
//do retention of M first
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "AminoAcid"))
{
begin--;
remove.Add(mod);
}
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "Missing"))
{
if (theoretical_base.sequence[this.begin - theoretical_base.begin].ToString() ==
mod.modification.Target.ToString())
{
begin++;
remove.Add(mod); //dont have in ptmset --> change the begin & end
}
else if (theoretical_base.sequence[this.end - this.begin].ToString() ==
mod.modification.Target.ToString())
{
end--;
remove.Add(mod);
}
}
foreach (var ptm in remove)
{
ptm_set.ptm_combination.Remove(ptm);
}
ptm_set = new PtmSet(ptm_set.ptm_combination);
if (e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) !=
this.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ||
e.begin != begin || e.end != end || !e.ptm_set.same_ptmset(ptm_set, true))
{
e.ambiguous = true;
Proteoform linked_proteoform_reference =
this.linked_proteoform_references == null || this.linked_proteoform_references.Count == 0
? this
: this.linked_proteoform_references.First();
Tuple <Proteoform, int, int, PtmSet> new_id =
new Tuple <Proteoform, int, int, PtmSet>(linked_proteoform_reference, begin, end, ptm_set);
lock (e.ambiguous_identifications)
{
if (!e.ambiguous_identifications.Any(p =>
p.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ==
new_id.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) &&
p.Item2 == new_id.Item2 && p.Item3 == new_id.Item3 &&
p.Item4.same_ptmset(new_id.Item4, true)))
{
e.ambiguous_identifications.Add(new_id);
}
}
}
}
if (this as ExperimentalProteoform != null && (this as ExperimentalProteoform).ambiguous)
{
foreach (var id in this.ambiguous_identifications)
{
TheoreticalProteoform id_theoretical_base = id.Item1 as TheoreticalProteoform;
int begin = id.Item2;
int end = id.Item3;
var remove = new List <Ptm>();
var ptm_set = determine_mod_change(e, this, id_theoretical_base, r, id.Item4);
if (ptm_set == null)
{
continue;
}
//do retention of M first
foreach (var mod in ptm_set.ptm_combination.Where(m => m.modification.ModificationType == "AminoAcid"))
{
begin--;
remove.Add(mod);
}
foreach (var mod in ptm_set.ptm_combination.Where(m => m.modification.ModificationType == "Missing"))
{
if (id_theoretical_base.sequence[id.Item2 - id.Item1.begin].ToString() == mod.modification.Target.ToString())
{
begin++;
remove.Add(mod); //dont have in ptmset --> change the begin & end
}
else if (id_theoretical_base.sequence[id.Item3 - id.Item2].ToString() == mod.modification.Target.ToString())
{
end--;
remove.Add(mod);
}
}
foreach (var ptm in remove)
{
ptm_set.ptm_combination.Remove(ptm);
}
ptm_set = new PtmSet(ptm_set.ptm_combination);
lock (e.ambiguous_identifications)
{
var new_id = new Tuple <Proteoform, int, int, PtmSet>(id.Item1, begin, end, ptm_set);
if ((e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) !=
new_id.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ||
e.begin != new_id.Item2 || e.end != new_id.Item3 || !e.ptm_set.same_ptmset(new_id.Item4, true)) &&
!e.ambiguous_identifications.Any(p =>
p.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ==
new_id.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) &&
p.Item2 == new_id.Item2 && p.Item3 == new_id.Item3 &&
p.Item4.same_ptmset(new_id.Item4, true)))
{
e.ambiguous_identifications.Add(new_id);
e.ambiguous = true;
}
}
}
}
e.uniprot_mods = "";
foreach (string mod in e.ptm_set.ptm_combination.Concat(e.ambiguous_identifications.SelectMany(i => i.Item4.ptm_combination)).Where(ptm => ptm.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m))
{
// positions with mod
List <int> theo_ptms = theoretical_base.ExpandedProteinList.First()
.OneBasedPossibleLocalizedModifications
.Where(p => p.Key >= e.begin && p.Key <= e.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
e.uniprot_mods += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (e.ptm_set.ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count ||
e.ambiguous_identifications.Any(i => i.Item4.ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count))
{
e.novel_mods = true;
}
}
//else if (!e.topdown_id && e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) != this.gene_name.get_prefered_name(Lollipop.preferred_gene_label)
// && e.linked_proteoform_references.Count == this.linked_proteoform_references.Count + 1)
//{
// e.ambiguous = true;
//}
}
public void identify_experimentals()
{
HashSet <ExperimentalProteoform> identified_experimentals = new HashSet <ExperimentalProteoform>();
if (Sweet.lollipop.identify_from_td_nodes)
{
foreach (TopDownProteoform topdown in experimental_proteoforms.Where(e => e.topdown_id))
{
Sweet.lollipop.theoretical_database
.theoreticals_by_accession[Sweet.lollipop.target_proteoform_community.community_number]
.TryGetValue(topdown.accession.Split('_')[0].Split('-')[0], out var t);
if (t != null && t.Count > 0)
{
TheoreticalProteoform theoretical =
new TheoreticalProteoform(topdown.accession, topdown.name, topdown.sequence,
t.First().ExpandedProteinList, topdown.modified_mass, topdown.lysine_count,
topdown.topdown_ptm_set, true, false, null);
theoretical.topdown_theoretical = true;
theoretical.new_topdown_proteoform = true;
theoretical.begin = topdown.topdown_begin;
theoretical.end = topdown.topdown_end;
foreach (ExperimentalProteoform e in topdown.identify_connected_experimentals(theoretical, topdown.topdown_begin, topdown.topdown_end,
new PtmSet(topdown.topdown_ptm_set.ptm_combination), null))
{
identified_experimentals.Add(e);
}
}
}
}
foreach (TheoreticalProteoform t in theoretical_proteoforms.OrderBy(t => t.topdown_theoretical))
{
lock (identified_experimentals)
foreach (ExperimentalProteoform e in t.identify_connected_experimentals(t, t.begin, t.end, t.ptm_set, t.linked_proteoform_references))
{
identified_experimentals.Add(e);
}
}
//Continue looking for new experimental identifications until no more remain to be identified
List <ExperimentalProteoform> newly_identified_experimentals = new List <ExperimentalProteoform>(identified_experimentals).OrderBy(p => p.relationships.Count(r => r.candidate_ptmset != null) > 0 ? p.relationships.Where(r => r.candidate_ptmset != null).Min(r => Math.Abs(r.DeltaMass - r.candidate_ptmset.mass)) : 1e6).ThenBy(p => p.modified_mass).ToList();
int last_identified_count = identified_experimentals.Count - 1;
while (newly_identified_experimentals.Count > 0) //&& identified_experimentals.Count > last_identified_count)
{
last_identified_count = identified_experimentals.Count;
HashSet <ExperimentalProteoform> tmp_new_experimentals = new HashSet <ExperimentalProteoform>();
foreach (ExperimentalProteoform id_experimental in newly_identified_experimentals)
{
{
lock (identified_experimentals) lock (tmp_new_experimentals)
foreach (ExperimentalProteoform new_e in id_experimental.identify_connected_experimentals(id_experimental.linked_proteoform_references.First() as TheoreticalProteoform, id_experimental.begin,
id_experimental.end, id_experimental.ptm_set, id_experimental.linked_proteoform_references))
{
identified_experimentals.Add(new_e);
tmp_new_experimentals.Add(new_e);
}
}
}
newly_identified_experimentals = new List <ExperimentalProteoform>(tmp_new_experimentals);
}
List <string> topdown_ids = Sweet.lollipop.topdown_proteoforms
.Select(p => p.accession.Split('_')[0].Split('-')[0] + "_" + p.sequence + "_" + string.Join(", ", p.topdown_ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m))).ToList();
//determine identified experimentals that are adducts
//checks if any experimentals have same mods as e's ptmset, except e has additional adduct only mods.
Parallel.ForEach(experimental_proteoforms, e =>
{
e.adduct =
e.linked_proteoform_references != null &&
e.ptm_set.ptm_combination.Any(m => Proteoform.modification_is_adduct(m.modification)) &&
experimental_proteoforms.Any(l =>
l.linked_proteoform_references != null &&
l.gene_name.get_prefered_name(Lollipop.preferred_gene_label) == e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) &&
l.ptm_set.ptm_combination.Count < e.ptm_set.ptm_combination.Count &&
e.ptm_set.ptm_combination.Where(m => l.ptm_set.ptm_combination.Count(p => UnlocalizedModification.LookUpId(p.modification) == UnlocalizedModification.LookUpId(m.modification)) != e.ptm_set.ptm_combination.Count(p => UnlocalizedModification.LookUpId(p.modification) == UnlocalizedModification.LookUpId(m.modification)))
.Count(p => !Proteoform.modification_is_adduct(p.modification))
== 0
);
if (e as TopDownProteoform != null)
{
(e as TopDownProteoform).set_correct_id();
}
if (e.linked_proteoform_references != null)
{
var mods = e.ptm_set.ptm_combination.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
e.uniprot_mods = "";
string add = "";
foreach (string mod in mods)
{
// positions with mod
List <int> theo_ptms = (e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= e.begin && p.Key <= e.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (e.ptm_set.ptm_combination.Where(ptm => ptm.modification.ModificationType != "Deconvolution Error" && !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
e.novel_mods = true;
}
}
e.uniprot_mods += add;
if (add.Length == 0)
{
e.uniprot_mods += "N/A";
}
foreach (var ambig_id in e.ambiguous_identifications)
{
var ambig_mods = ambig_id.ptm_set.ptm_combination.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
e.uniprot_mods += " | ";
add = "";
foreach (var mod in ambig_mods)
{
// positions with mod
List <int> theo_ptms = ambig_id.theoretical_base.ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= ambig_id.begin && p.Key <= ambig_id.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (ambig_id.ptm_set.ptm_combination.Where(ptm => ptm.modification.ModificationType != "Deconvolution Error" && !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
e.novel_mods = true;
}
}
e.uniprot_mods += add;
if (add.Length == 0)
{
e.uniprot_mods += "N/A";
}
}
}
//determine level #
e.proteoform_level_description = "";
if (e.linked_proteoform_references == null)
{
e.proteoform_level = 5;
e.proteoform_level_description = "Unidentified";
}
else if (e.ambiguous_identifications.Count == 0)
{
if (e.ptm_set.ptm_combination.Count == 0)
{
e.proteoform_level = 1;
}
else
{
e.proteoform_level = 2;
e.proteoform_level_description += "PTM localization ambiguity; ";
}
//check if accessions had been grouped in constructing the theoretical database
if ((e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.AccessionList).Select(a => a.Split('_')[0]).Distinct().Count() > 1)
{
e.proteoform_level += 1;
e.proteoform_level_description += "Gene ambiguity; ";
}
}
else
{
var unique_accessions = new List <string>()
{
e.linked_proteoform_references.First().accession.Split('_')[0].Split('-')[0]
}.Concat(e.ambiguous_identifications.Select(a => a.theoretical_base.accession.Split('_')[0].Split('-')[0])).Distinct();
var unique_sequences = new List <string>()
{
ExperimentalProteoform.get_sequence(e.linked_proteoform_references.First() as TheoreticalProteoform, e.begin, e.end)
}.
Concat(e.ambiguous_identifications.Select(a => ExperimentalProteoform.get_sequence(a.theoretical_base, a.begin, a.end))).Distinct();
var unique_PTMs = new List <string>()
{
string.Join(", ", e.ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m))
}.Concat(e.ambiguous_identifications.Select(a => string.Join(", ", a.ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))))).Distinct();
int gene_ambiguity = unique_accessions.Count() > 1 ? 1 : 0;
//check if accessions had been grouped in constructing the theoretical database
if ((e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.AccessionList).Select(a => a.Split('_')[0]).Distinct().Count() > 1)
{
gene_ambiguity = 1;
}
int sequence_ambiguity = unique_sequences.Count() > 1 ? 1 : 0;
int PTM_ambiguity = unique_PTMs.Count() > 1 ? 1 : 0;
int PTM_location = e.ptm_set.ptm_combination.Count(m => m.modification.ModificationType != "Deconvolution Error") > 0 || e.ambiguous_identifications.Any(a => a.ptm_set.ptm_combination.Count(m => m.modification.ModificationType != "Deconvolution Error") > 0) ? 1 : 0;
e.proteoform_level = 1 + gene_ambiguity + sequence_ambiguity + PTM_ambiguity + PTM_location;
if (gene_ambiguity > 0)
{
e.proteoform_level_description += "Gene ambiguity; ";
}
if (sequence_ambiguity > 0)
{
e.proteoform_level_description += "Sequence ambiguity; ";
}
if (PTM_ambiguity > 0)
{
e.proteoform_level_description += "PTM identity ambiguity; ";
}
if (PTM_location > 0)
{
e.proteoform_level_description += "PTM localization ambiguity; ";
}
}
if (e.proteoform_level == 1)
{
e.proteoform_level_description = "Unambiguous";
}
//determine if new intact-mass ID
e.new_intact_mass_id = false;
if (!e.topdown_id && e.linked_proteoform_references != null && e.ambiguous_identifications.Count == 0)
{
string this_id = string.Join(",", (e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.AccessionList.Select(a => a.Split('_')[0])).Distinct()) + "_" + ExperimentalProteoform.get_sequence(e.linked_proteoform_references.First() as TheoreticalProteoform, e.begin, e.end) + "_" + string.Join(", ", e.ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m));
if (!topdown_ids.Any(t => this_id.Split('_')[0].Split(',').Contains(t.Split('_')[0]) &&
this_id.Split('_')[1] == t.Split('_')[1] && this_id.Split('_')[2] == t.Split('_')[2]))
{
e.new_intact_mass_id = true;
}
}
});
if (Sweet.lollipop.remove_bad_connections)
{
if (theoretical_proteoforms.Count > 0 || (Sweet.lollipop.identify_from_td_nodes && experimental_proteoforms.Count(e => e.topdown_id) > 0))
{
Parallel.ForEach(relations, r =>
{
r.Accepted = r.Identification;
});
}
}
}